Plasminogen activators in normal tissue and carcinomas of the human oesophagus and stomach.

Sier, Cornelis F.M.; Verspaget, Hein W.; Griffioen, G.; Ganesh, S.; Vloedgraven, H. J. M.; Lamers, C. B. H. W.

doi:10.1136/gut.34.1.80

Cited by 59 publications

(22 citation statements)

References 25 publications

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“…The role of ADH7 in steroid and fat metabolism is also interesting in this disease because of the association with diet, overweight and obesity. 4 We confirm the previously reported reduced expression for the genes PAI-2 (plasminogen activator inhibitor type-2), 37,38 GSTP1 (glutathione S-transferase pi), 39 RB1 (retinoblastoma) 40 and PITX1 (pituitary homeobox 1). 9,24 Of note, PAI-2 expression was more than 100 times lower in EAC than normal esophagus.…”

Section: Discussionsupporting

confidence: 90%

Gene expression alterations in formalin-fixed, paraffin-embedded Barrett esophagus and esophageal adenocarcinoma tissues.

Botelho¹,

Schneiders²,

Lord³

et al. 2010

Cancer Biology & Therapy

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Section: Discussionsupporting

confidence: 90%

Gene expression alterations in formalin-fixed, paraffin-embedded Barrett esophagus and esophageal adenocarcinoma tissues.

Botelho¹,

Schneiders²,

Lord³

et al. 2010

Cancer Biology & Therapy

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“…Because of the fact that these PA parameters could discem patients at high risk of developing recurrent disease or having a poor survival in the node-negative group, they already form the basis for selection of patients for further treatment with chemotherapy. Also, high levels of u-PA, PAI-I and PAI-2 have been found in carcinomas of the stomach and oesophagus (Nishino et al, 1988;Takai et al, 1991;Tanaka et al, 1991;Nakamura et al, 1992;Sier et al, 1993b). Moreover, recent reports of Nekarda et al (1994), Heiss et al (1995), and our group (Ganesh et al, 1996) have shown that these parameters are of prognostic value for the survival of patients with gastric cancer, PAI-1 being an independent prognostic factor.…”

Section: Discussionsupporting

confidence: 52%

Contribution of plasminogen activators and their inhibitors to the survival prognosis of patients with Dukes' stage B and C colorectal cancer

Ganesh

Sier²,

Heerding³

et al. 1997

Br J Cancer

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Summary Despite the advances in pre-, peri-and post-operative medical care of colorectal carcinoma patients, the prognosis has improved only marginally over recent decades. Thus, additional prognostic indicators would be of great clinical value to select patients for adjuvant therapy. In previous studies we found that colorectal carcinomas have a marked increase of the urokinase-type of plasminogen activator (u-PA), and the inhibitors PAI-1 and PAI-2, whereas the tissue-type plasminogen activator (t-PA) is found to be decreased in comparison with adjacent normal mucosa. In the present study we evaluated the prognostic value of several plasminogen activation parameters, determined in both normal and carcinomatous tissue from colorectal resection specimens, for overall survival of 136 Dukes' stage B and C colorectal cancer patients, in relation to major clinicopathological parameters. Uni-and multivariate analyses indicated that a high PAI-2 antigen level in carcinoma, a low t-PA activity and antigen level and a high u-PA/t-PA antigen ratio in adjacent normal mucosa are significantly associated with a poor overall survival. A high ratio of u-PA antigen in the carcinomas and t-PA antigen in normal mucosa, i.e. u-PA(C)/t-PA(N), was found to be predictive of a poor overall survival as well. All these parameters were found to be prognostically independent of the clinicopathological parameters. Multivariate analysis of combinations of these prognostically significant plasminogen activation parameters revealed that they are important independent prognostic indicators and have in fact a better prognostic value than their separate components. Based on these combined parameters, subgroups of patients with Dukes' stage B and C colorectal cancer could be identified as having either a high or a low risk regarding overall survival. In conclusion, these findings emphasize the relevance of the intestinal plasminogen activation system for survival prognosis of patients with colorectal cancer and, in the future, might constitute a patient selection criterion for adjuvant therapy.

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“…The duality of this system allows a plasticity not present in the protease system alone. This plasticity may be particularly relevant in disease states characterized by accumulation of vitronectin and PAI-1, such as atheroma (27, 51), acute inflammatory reactions in the lung (9,26), and several cancerous states (52)(53)(54)(55)(56)(57). Excess PAI-1, while promoting persistence of fibrin and subsequent scarification (47), may also promote inflammatory and tumor cell mobility within the provisional matrix.…”

Section: Discussionmentioning

confidence: 99%

Plasmin and plasminogen activator inhibitor type 1 promote cellular motility by regulating the interaction between the urokinase receptor and vitronectin.

Waltz

Natkin²,

Fujita³

et al. 1997

J. Clin. Invest.

258

205

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The urokinase receptor (uPAR) coordinates plasmin-mediated cell-surface proteolysis and promotes cellular adhesion via a binding site for vitronectin on uPAR. Because vitronectin also binds plasminogen activator inhibitor type 1 (PAI-1), and plasmin cleavage of vitronectin reduces PAI-1 binding, we explored the effects of plasmin and PAI-1 on the interaction between uPAR and vitronectin. PAI-1 blocked cellular binding of and adhesion to vitronectin by over 80% (IC 50 ‫ف‬ 5

show abstract

Plasminogen activators in normal tissue and carcinomas of the human oesophagus and stomach.

Cited by 59 publications

References 25 publications

Gene expression alterations in formalin-fixed, paraffin-embedded Barrett esophagus and esophageal adenocarcinoma tissues.

Gene expression alterations in formalin-fixed, paraffin-embedded Barrett esophagus and esophageal adenocarcinoma tissues.

Contribution of plasminogen activators and their inhibitors to the survival prognosis of patients with Dukes' stage B and C colorectal cancer

Plasmin and plasminogen activator inhibitor type 1 promote cellular motility by regulating the interaction between the urokinase receptor and vitronectin.

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